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AIMS To assess the efficacy and safety of iGlarLixi (the titratable fixed-ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol). MATERIALS AND METHODS The LixiLan-O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan-O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening. RESULTS The mean diabetes duration was 10.0 years, and the mean duration of second OAD use was 4.5 years. iGlarLixi demonstrated greater mean reductions from baseline in HbA1c and 2-hour postprandial glucose (PPG) compared with iGlar or Lixi (HbA1c -1.9% vs. -1.6% or -1.0% [-20 vs. -17 or -10 mmol/mol; 2-hour PPG -7.2 vs. -4.6 or -5.5 mmol/L). Greater proportions of participants achieved HbA1c

Summary Background Extreme heat exposure can lead to premature death. Climate change is expected to increase the frequency, intensity, and duration of extreme heat events, resulting in many additional heat-related deaths globally, as well as changing the nature of extreme cold events. At the same time, vulnerability to extreme heat has decreased over time, probably due to a combination of physiological, behavioural, infrastructural, and technological adaptations. We aimed to account for these changes in vulnerability and avoid overstated projections for temperature-related mortality. We used the historical observed decrease in vulnerability to improve future mortality estimates. Methods We used historical mortality and temperature data from 208 US cities to quantify how observed changes in vulnerability from 1973 to 2013 affected projections of temperature-related mortality under various climate scenarios. We used geographically structured meta-regression to characterise the relationship between temperature and mortality for these urban populations over the specified time period. We then used the fitted relationships to project mortality under future climate conditions. Findings Between Oct 26, 2018, and March 9, 2020, we established that differences in vulnerability to temperature were geographically structured. Vulnerability decreased over time in most areas. US mortalities projected from a 2°C increase in mean temperature decreased by more than 97% when using 2003–13 data compared with 1973–82 data. However, these benefits declined with increasing temperatures, with a 6°C increase showing only an 84% decline in projected mortality based on 2003–13 data. Interpretation Even after accounting for adaptation, the projected effects of climate change on premature mortality constitute a substantial public health risk. Our work suggests large increases in temperature will require additional mitigation to avoid excess mortality from heat events, even in areas with high air conditioning coverage in place. Funding The US Environmental Protection Agency and Abt Associates.

People with type 1 diabetes who met NHS England funding criteria attended an accredited, intensive one-day structured education programme and completed the online FreeStyle Libre Academy training module followed by a 30-minute healthcare professional face-to-face practical training session. HbA1c, Gold hypoglycaemia score and Diabetes Distress Screening score were documented before commencement of the intervention and at 6 months. 213 people with type 1 diabetes (52% men; average age 48 years (range 18–87)) completed the 6-month intervention. Overall mean HbA1c reduced by 6 mmol/mol (0.5%) from 62±14 mmol/mol (7.8%) to 56±12 mmol/mol (7.3%) (p

To describe the phase 3a ONWARDS clinical development programme investigating insulin icodec (icodec), a once-weekly basal insulin, including the design and rationale for each of the ONWARDS 1-6 trials.Six randomized controlled trials have been initiated in adults with type 2 diabetes (T2D) (insulin-naive: ONWARDS 1, 3 and 5; previously insulin-treated: ONWARDS 2 and 4) and type 1 diabetes (T1D) (ONWARDS 6). Each trial will investigate icodec use in a unique clinical scenario, with consideration of long-term safety and varied comparator treatments (insulin glargine U100 or U300 or insulin degludec). ONWARDS 5 will incorporate real-world elements and a digital dose titration solution to guide icodec dosing. The primary objective for each of the trials is to compare the change in HbA1c from baseline to week 26 or week 52 between icodec and comparator arms. Secondary objectives include investigating other glycaemic control and safety parameters, such as fasting glucose, time in glycaemic range and hypoglycaemia. Patient-reported outcomes will assess treatment satisfaction.The ONWARDS 1-6 trials will evaluate the efficacy and safety of once-weekly icodec compared with currently available daily basal insulin analogues in T2D and T1D. These trials will generate comprehensive evidence of icodec use in diverse populations across the spectrum of diabetes progression and treatment experience.

Objective This work aimed to investigate the effect of the SGLT2 inhibitor, dapagliflozin (DAPA), on cardiac function and the metabolic and hormonal response to moderate exercise in people with type 2 diabetes. Methods This was a double-blind, placebo-controlled crossover study with a 4-week washout period. Nine participants were randomly assigned to receive either 4 weeks of DAPA or 4 weeks of placebo. After each treatment, they underwent an exercise protocol with 2 consecutive 10-minute stages at a constant load corresponding to 40% and 70% maximal oxygen consumption (VO2max), coupled with hormonal and metabolic analysis. A blinded transthoracic echocardiogram was performed 3 days later. Results During the exercise protocol, glucose and lactate were lower (P < .0001 and P < .05, respectively) and β-hydroxybutyrate (BOBH) and growth hormone (GH) were higher (P < .0005 and P = .01) following DAPA treatment compared to placebo. There was a trend for lower insulin with DAPA. Adrenalin, noradrenalin, and glucagon were not different. Following DAPA participants demonstrated an increased mean peak diastolic mitral annular velocity (e’) in comparison to placebo (P = .03). The indexed left atrial volume and right ventricular e” were reduced following DAPA compared with placebo (P = .045 and P = .042, respectively). Arterial stiffness was not different between treatments (DAPA 9.35 ± 0.60 m/s; placebo 9.07 ± 0.72 m/s). Conclusion During exercise, GH may be more important than catecholamines in driving the shift from glucose to fatty acid metabolism by SGLT2 inhibitors. The 4-week crossover design showed changes in cardiac function were rapid in onset and reversible.

This dataset includes the numpy arraysused inplotting the figures in the paper: "Radiation, Clouds, and Self-Aggregation in RCEMIP Simulations". Each zipped file contains the arrays used to create one figure. The units are always SI. A description of the format of each array is given below. Fig01 "_cloud_components_for_.npy" Has shape (n_cloud_types, n_CRMs) Cloud types are in the same order as displayed on the x-axis of the figure. CRMs are in order of those displayed in figure 3. DAM and MESONH are missing due to not having 3D data. Fig02 "__cloud_fraction_vs_FMSE.npy" Shape = (100, ) 100 FMSE percentiles from 0 to 99, 4 or 8 cloud types depending on the cloud scheme. Value shows fraction of cloud type at that FMSE percentile. Fig03 & Fig04 "__var_normFMSE.npy" Time series of var(hn) without any smoothing in time. First 2 days (8 time steps) are not included. Fig05 "___budget-terms.npy" Shape = (5, n_models) First dimension is var(hn) term, LW term, SW term, SEF term, Advection term. Models are in order of those shown in figures 3 and 4 depending on the model_type. "___budget-terms_ClearSky.npy" Shape = (2, n_models) First dimension is LW term, SW term. Fig06 Each subplot can be made by plotting the arrays on either the x or y axis. Fig07 & Fig08 "___.npy" shape = (4, n_models) first dimension is the cloud types: Clear, Shallow, Other, Deep models in the same order as shown in figures 3 or 4 depending on the model_type. &nbsp

Background The pathophysiology of COVID-19 remains poorly understood. We aimed to estimate the contribution of intrapulmonary shunting and ventilation-to-perfusion (VA/Q) mismatch using a mathematical model to construct oxygen-haemoglobin dissociation curves (ODCs). Methods ODCs were constructed using transcutaneous pulse oximetry at two different fractions of inspired oxygen (FiO2). 199 patients were included from two large district general hospitals in the South East of England from 1st to 14th January 2021. The study was supported by the National Institute of Health Research (NIHR) Clinical Research Network. Results Overall mortality was 29%. Mean age was 68.2 years (SEM 1·2) with 46% female. Median shunt on admission was 17% (IQR 8–24.5); VA/Q was 0.61 (IQR 0.52–0.73). Shunt was 37.5% higher in deaths (median 22%, IQR 9–29) compared to survivors (16%, 8–21; p = 0.0088) and was a predictor of mortality (OR 1.04; 95% CI 1.01–1.07). Admission oxygen saturations were more strongly predictive of mortality (OR 0.91, 95% CI 0.87–0.96). There was no difference in VA/Q mismatch between deaths (0.60; IQR 0.50–0.73) and survivors (0.61; IQR 0.52–0.73; p = 0.63) and it was not predictive of mortality (OR 0.68; 95% CI 0.18–2.52; p = 0.55). Shunt negatively correlated with admission oxygen saturation (R -0.533; pA/Q was not (R 0.1137; p = 0.12). Interpretation Shunt, not VA/Q mismatch, was associated with worsening hypoxia, though calculating shunt was not of prognostic value. This study adds to our understanding of the pathophysiology of hypoxaemia in COVID-19. Our inexpensive and reliable technique may provide further insights into the pathophysiology of hypoxia in other respiratory diseases.

BACKGROUND: This retrospective cohort study aims to define the clinical findings and outcomes of every patient admitted to a district general hospital in Surrey with COVID-19 in March 2020, providing a snapshot of the first wave of infection in the UK. This study is the first detailed insight into the impact of frailty markers on patient outcomes and provides the infection rate among healthcare workers. METHODS: Data were obtained from medical records. Outcome measures were level of oxygen therapy, discharge and death. Patients were followed up until 21 April 2020. RESULTS: 108 patients were included. 34 (31%) died in hospital or were discharged for palliative care. 43% of patients aged over 65 died. The commonest comorbidities were hypertension (49; 45%) and diabetes (25; 23%). Patients who died were older (mean difference ±SEM, 13.76±3.12 years; p

OBJECTIVE The risk of hypoglycemia in people with insulin-treated diabetes has debarred them from certain “safety-critical” occupations, including flying commercial aircraft. This report evaluates the effectiveness of a protocol enabling a large cohort of insulin-treated pilots to fly commercially. RESEARCH DESIGN AND METHODS This was an observational study of pilots with insulin-treated diabetes who were granted medical certification to fly commercial and noncommercial aircraft. Clinical details, pre- and in-flight (hourly and 30 min before landing) blood glucose values were correlated against the protocol-specified ranges: green (5–15 mmol/L), amber (low, 4–4.9 mmol/L; high, 15.1–20 mmol/L), and red (low, 20 mmol/L). RESULTS A total of 49 pilots with type 1 (84%) or type 2 (16%) diabetes who had been issued class 1 or class 2 certificates were studied. Median diabetes duration was 10.9 years. Mean HbA1c was 7.2% (55.0 mmol/mol) before certification and 7.2% (55.1 mmol/mol) after certification (P = 0.97). Blood glucose values (n = 38,621) were recorded during 22,078 flying hours. Overall, 97.69% of measurements were within the green range, 1.42% within the low amber range, and 0.75% within the high amber range. Only 0.12% of readings were within the low red range and 0.02% within the high red range. Out-of-range readings declined from 5.7% in 2013 to 1.2% in 2019. No episodes of pilot incapacitation occurred, and glycemic control did not deteriorate. CONCLUSIONS The protocol is practical to implement, and no events compromising safety were reported. This study represents what is, to our knowledge, the most extensive data set from people with insulin-treated diabetes working in a “safety-critical” occupation, which may be relevant when estimating risk in other safety-critical occupations.

Sodium glucose cotransporter 2 (SGLT2) inhibitors are the latest class of oral hypoglycaemic agents approved to treat type II diabetes. Their use is increasing and as such more patients will present to critical care whilst on this treatment. However, there have been several case reports of euglycaemic diabetic ketoacidosis associated with the use of these agents. Under such circumstances the blood glucose is often normal or only moderately elevated and hence the diagnosis may be delayed resulting in inappropriate therapy. In this review we describe a case of SGLT2 mediated ketoacidosis who presented to our intensive care unit, discuss the proposed pathophysiology behind this development of ketoacidosis as well as its potential prevention, management and treatment.

OBJECTIVE To investigate the mechanism for increased ketogenesis following treatment with the SGLT2 inhibitor dapagliflozin in people with type 2 diabetes. RESEARCH DESIGN AND METHODS The design was a double-blind, placebo-controlled, crossover study with a 4-week washout period. Participants received dapagliflozin or placebo in random order for 4 weeks. After each treatment, they ingested 30 mL of olive oil containing [U-13C]palmitate to measure ketogenesis, with blood sampling for 480 min. Stable isotopes of glucose and glycerol were infused to measure glucose flux and lipolysis, respectively, at 450–480 min. RESULTS Glucose excretion rate was higher and peripheral glucose uptake lower with dapagliflozin than placebo. Plasma β-hydroxybutyrate (BOHB) concentrations and [13C2]BOHB concentrations were higher and glucose concentrations lower with dapagliflozin than placebo. Nonesterified fatty acids (NEFAs) were higher with dapagliflozin at 300 and 420 min, but lipolysis at 450–480 min was not different. Triacylglycerol at all time points and endogenous glucose production rate at 450–480 min were not different between treatments. CONCLUSIONS The increase in ketone enrichment from the ingested palmitic acid tracer suggests that meal-derived fatty acids contribute to the increase in ketones during treatment with dapagliflozin. The increase in BOHB concentration with dapagliflozin occurred with only minimal changes in plasma NEFA concentration and no change in lipolysis. This finding suggests a metabolic switch to increase ketogenesis within the liver.

The discovery of insulin 100 years ago ranks among the greatest medical achievements ever. This sparked a revolution of scientific discovery and therapeutic intervention to treat people suffering with diabetes. A light was shone for other areas of medicine to illuminate what was possible with detailed scientific endeavour. There followed a range of firsts leading to the current time in which we now know more about this peptide hormone than almost any other protein in existence. This has allowed therapeutic advancement from a positon of knowledge leading to stunning innovation. This innovation is likely to lead to more physiological insulin replacement reducing the disease burden to individuals and society as whole.

It has been known for over 40 years that dietary insufficiency of vitamin B12 in pregnant mothers can lead to vitamin B12 deficiency in the children and is often accompanied by developmental delay. In a previous study we found a deficiency of functional vitamin B2 in each members of a cohort 600 children and adults with a diagnosis of Autism Spectrum Disorder (ASD) of various ages (18 months to 34 years). The same cohort has also been assessed for functional vitamin B12 and each member of the cohort assessed was found to have functional vitamin B12 deficiency. The functional deficiency appeared to be related to the functional B2 deficiency, that was attributed to insufficient dietary Iodine, Selenium and/or Molybdenum. The functional B12 deficiency occurred despite elevated serum B12 being found, and hence presents as Paradoxical vitamin B12 deficiency. As such, ASD due to functional B2 deficiency results in Paradoxical B12 deficiency, which differs from classical developmental delay due to vitamin B12 deficiency, as the later is correctable by administration of vitamin B12 alone. In contrast, ASD due to Paradoxical vitamin B12 deficiency, requires resolution of functional B2 deficiency before treatment with vitamin B12 can be effective.

The pollution of marine environments from plastic waste is anticipated to increase with current increases in plastic production. Reciprocally, escalating research efforts provide an improved understanding, monitoring, awareness, and mitigation of plastic contamination. Freshwater streams are recognised as one of the main contributors of microplastic pollution in marine environments. Presented here is the first investigation on the abundance of microplastic contamination (20 μm and5 mm) in freshwater streams in Adelaide, Australia. Composite samples were obtained from the sub-surface waters of eight freshwater streams (Magazine Wetland, Torrens River, Brownhill Creek, Sturt River, Field River, Christie Creek, Onkaparinga River and Pedler Creek), just before their connection to the Gulf St Vincent. Microplastics were found in all samples and microplastic abundance was 6.4 ± 5.5 particles.L

Purpose The purpose of this paper is to perform and report a systematic review of published research on patient safety attitudes of health staff employed in hospital emergency departments (EDs). Design/methodology/approach An electronic search was conducted of PsychINFO, ProQuest, MEDLINE, EMBASE, PubMed and CINAHL databases. The review included all studies that focussed on the safety attitudes of professional hospital staff employed in EDs. Findings Overall, the review revealed that the safety attitudes of ED health staff are generally low, especially on teamwork and management support and among nurses when compared to doctors. Conversely, two intervention studies showed the effectiveness of team building interventions on improving the safety attitudes of health staff employed in EDs. Research limitations/implications Six studies met the inclusion criteria, however, most of the studies demonstrated low to moderate methodological quality. Originality/value Teamwork, communication and management support are central to positive safety attitudes. Teamwork training can improve safety attitudes. Given that EDs are the “front-line” of hospital care and patients within EDs are especially vulnerable to medical errors, future research should focus on the safety attitudes of medical staff employed in EDs and its relationship to medical errors.

Executive SummaryA backlash against numerous inequalities – and in particular against perceived unfairness in society – is a significant driver of the UK's current political malaise. Addressing inequalities between income groups, regions and generations will thus be key to re-establishing faith in government and avoiding further decline or even the threat of social unrest.In income terms, the UK has become much more unequal than in the immediate post-war decades, and it should be a goal to reverse that trend – targeting the OECD average for income inequality and a halving of the number of those living below the poverty line. Measures to deal with perceived unfairnesses could include tighter scrutiny of competition in high-yielding sectors such as technology, and incentives for the appointment of worker representatives to company boards. But a government intent on tackling inequalities will inescapably need to raise public spending and direct taxation of income and capital from their current historically low levels. In particular spending on education and active labour market policies needs to increase, while gaps in the benefits system and regional imbalances are addressed.Given the scale of technological change and the severe implications for the labour market, the risk is that policy will be insufficiently bold to deal with widespread disenchantment, which could ultimately pose a threat to democracy.

Executive SummaryThe UK economy faces more than usually uncertain times. Outside the European Union, and in an increasingly challenging global environment characterised by ageing populations, climate change, populism, protectionism, and more, the country needs to chart a new course. This may well require policymakers to consider unconventional approaches to monetary and fiscal policy and, at the very least argues for important modifications of the current policy regime, including the autonomous mandate of the Bank of England.At some point, there will be a major slowdown in economic activity. Yet the Bank of England has very little leeway to respond by cutting interest rates, and it has already adopted an armoury of unorthodox tools that may be decreasing in effectiveness. More radical monetary approaches would be likely to be politically controversial; and are not without risks. In these circumstances it would be a mistake to rely solely, or even largely, on monetary policy to maintain demand. It would be better to conduct monetary and fiscal policy in tandem, and for discretionary fiscal policy to be required to play a much more active role in demand management than hitherto. This would, for example, imply major extension of the automatic stabilisers and efforts better to calibrate discretionary initiatives with the business cycle.But given the long-term pressures on the public finances, more fundamental changes in the structure of spending and taxation are needed, along with a redrawing of fiscal rules and targets, under independent budgetary oversight. The current, historically low, share in GDP of public spending is itself unsustainable in light of the demand for services of an ageing population; plans should be made to raise it closer to the European average. In the most extreme circumstances it might become necessary to waive the fiscal rules entirely and for the Bank of England directly to underwrite fiscal stimulus in order to sustain aggregate demand. It would be wise for the authorities to consider the options in detail now, while the environment is still relatively stable.

Executive SummaryInfrastructure investment can substantially increase a nation's capital stock and thereby boost productive, or supply-side, potential. It can also be useful as a tool in macroeconomic stabilisation, while public spending on quality infrastructure projects has been shown to have significantly greater multiplier effects than tax cuts – so the case for an increasing spend is not undermined by a country's overall debt level.These arguments are especially apposite for post-Brexit UK. Britain's investment performance in general has been especially poor since the 2016 EU referendum. Fixed capital formation as a proportion of GDP is low by international standards, while the government's share of fixed capital formation, at 2.5 per cent, is also below average. It would make sense to target an increase in public and private infrastructure spend to 3.5 per cent of GDP which is the OECD's recommended level.While major infrastructure projects continue to generate controversy on grounds of cost overruns and other issues, UK policy-makers have recently taken a more constructive approach to infrastructure development, notably with the creation of an independent National Infrastructure Commission.But the UK's infrastructure remains unsatisfactory, with significant parts of its energy, water, transport and communications networks in need of renewal or replacement, and infrastructure project delivery remains poor. In summary, much of Britain continues to operate well into the 21st century largely with 20th century, sometimes 19th century, infrastructure assets that are creating bottlenecks, crimping productivity, putting off potential foreign investors, undermining the economy's competitiveness, increasing inequality, and leaving the economy ill-equipped to face future challenges such as Brexit and climate change.The government needs to be bolder, setting out a more ambitious set of priorities including energy projects, regional spending, and fostering capital recycling and private sector investment. A still more ambitious, but eminently feasible, proposal would be to establish a National Investment Bank to offer project guarantees, recommend user fees, lend to projects with the proceeds of National Investment Bonds and simplify planning among other tasks. In a serious downturn, with monetary policy exhausted, the NIB could also help to co-ordinate and finance a response.

Introduction: People with diabetes in hospital have longer lengths of stay and are at higher risk of experiencing avoidable harm. This has a significant impact on patient flow and capacity in any hospital Trust.Aims and Methods: A Trust-wide peripatetic inpatient diabetes service redesign was performed to deliver reduced medication errors, improved patient flow, reduced length of stay and reduced inpatient risk. The service redesign was delivered without new recurring expenditure on senior staff. The model of care was multidisciplinary and introduced consensus and evidence-based care with clear governance processes.Results: Following introduction of the new service on 7 December 2017 to 1 June 2018, a reduction in length of stay in both medicine and surgical divisions was seen with 2,168 ‘saved’ inpatient bed days compared with the same time period in the preceding year, which represented a significant cost saving for the Trust and improvement in patient flow. This was associated with a reduction in the number of diabetes-related Datix reports and serious untoward incidents.Conclusions: This is the first major diabetes service redesign in a small district general hospital. The introduction of a dedicated inpatient diabetes service has led to Trust-wide improvements in patient care and patient flow without additional cost to the Trust.

Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic p53 activator with oral administration. To determine the need to conduct dedicated trial(s) for organ impairment on pharmacokinetic (PK) exposure and/or drug–drug interactions, a single dose of [14C]- and [13C]-labeled idasanutlin was evaluated. This study was an open-label, non-randomized, single-center trial of idasanutlin to investigate the excretion balance, pharmacokinetics, metabolism, and absolute bioavailability of a single oral dose of [14C]-labeled idasanutlin and an IV tracer dose of [13C]-labeled idasanutlin in a single cohort of patients with solid tumors. After completing cycle 1 assessments, patients could have participated in an optional treatment extension of idasanutlin. Clinical endpoints were PK, and safety/tolerability. Co-administration of an oral dose of idasanutlin with an IV tracer dose revealed low systemic CL, a moderate Vd, and a moderate (40.1%) absolute bioavailability of idasanutlin. Idasanutlin and its major inactive metabolite, M4, were the major circulating moieties in plasma, and excretion of idasanutlin-associated radioactivity was primarily via the fecal route (91.5% of the dose), with negligible amounts recovered in urine, following oral administration. The clinical implications of this study support the conclusion that renal impairment is unlikely to significantly impact exposure to idasanutlin and M4 metabolite, whereas a significant hepatic impairment may potentially alter exposure to the parent drug and/or metabolite(s). The potential for drug–drug interactions is low.

Aim To compare the efficacy and safety of self‐ versus physician‐managed titration of insulin glargine 300 U/mL (Gla‐300) in people with inadequately controlled type 2 diabetes. Methods Take Control (EudraCT number: 2015‐001626‐42) was a 24‐week, multi‐national, open‐label, controlled, two‐arm, parallel‐group study in insulin‐naïve and pre‐treated participants, randomized 1:1 to a self‐ or physician‐managed titration of Gla‐300. The fasting self‐monitored plasma glucose (SMPG) target was 4.4 to 7.2 mmol/L. The primary outcome was non‐inferiority of glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary outcomes included SMPG target achievement without hypoglycaemia, hypoglycaemia incidence, adverse events and participant‐reported outcomes (PROs). Results At week 24, the least squares (LS) mean HbA1c reduction was 0.97% (10.6 mmol/mol) and 0.84% (9.2 mmol/mol) in the self‐ and physician‐managed groups, respectively, with an LS mean difference of −0.13% [95% confidence interval −0.2619 to −0.0004] (–1.4 mmol/mol [–2.863 to –0.004]), demonstrating non‐inferiority (P

To assess the efficacy and safety of iGlarLixi (the titratable fixed-ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol).The LixiLan-O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan-O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening.The mean diabetes duration was 10.0 years, and the mean duration of second OAD use was 4.5 years. iGlarLixi demonstrated greater mean reductions from baseline in HbA1c and 2-hour postprandial glucose (PPG) compared with iGlar or Lixi (HbA1c -1.9% vs. -1.6% or -1.0% [-20 vs. -17 or -10 mmol/mol; 2-hour PPG -7.2 vs. -4.6 or -5.5 mmol/L). Greater proportions of participants achieved HbA1c7% (53 mmol/mol) with iGlarLixi versus iGlar or Lixi (67% vs. 51% or 18%), and the composite endpoints of HbA1c7% (53 mmol/mol) with no body weight gain (36% vs. 19% or 16%), and HbA1c7% (53 mmol/mol) with no body weight gain and no documented symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L; 28% vs. 15% or 15%). The incidence rates of documented symptomatic hypoglycaemia were 29.0%, 27.9% and 12.1% for iGlarLixi, iGlar and Lixi, respectively.Adults with T2D and HbA1c ≥64 mmol/mol (≥8%) despite two OADs at screening achieved better glycaemic control with iGlarLixi versus iGlar or Lixi, without increased risk of hypoglycaemia versus iGlar.

AIM To examine blood glucose measurements recorded as part of the diabetes protocol operated by the UK, Ireland and Austria, which allows commercial airline pilots with insulin-treated diabetes to fly. METHODS An observational study was conducted in pilots with insulin-treated diabetes, granted medical certification to fly commercial or noncommercial aircraft, who recorded pre-flight and hourly in-flight blood glucose measurements. These values were correlated to a traffic light system (green 5.0 to 15.0 mmol/L; amber 4.0 to 4.9 mmol/L and 15.1 to 20.0 mmol/L; and red 20.0 mmol/L) and studied for trends in glucose concentrations, time course within flight and any consequences. Pilot demographics were also analysed. RESULTS Forty-four pilots (90%) recorded one or more blood glucose value outside the green range during the 7 years of the study. Pilot age, diabetes type and duration, and follow-up period were comparable among subgroups, and mean glycated haemoglobin did not differ before and after certification in a way which would indicate poorer glycaemic control in any subgroup. A total of 892 blood glucose values (2.31%) were outside the green range, with half reported in-flight at various time intervals. There were 48 (0.12%) low red range values recorded, 14 (0.04%) of which occurred in-flight; all but four were restored to within the green range by the time of the next measurement. Appropriate corrective action was taken for all out-of-range values, with no reports of pilot incapacitation from any cause. CONCLUSIONS The traffic light system appears effective in identifying and reducing the frequency and severity of out-of-range values.

People with diabetes treated with insulin have often faced blanket bans from safety-critical occupations, largely because of fear of incapacitation due to hypoglycaemia. Recent advances in insulin therapies, modes of administration, monitoring, and noninvasive monitoring techniques have allowed stereotypical views to be challenged. The aviation sector has led the way, in allowing pilots to fly while on insulin. Recently, countries that have traditionally been opposed to this have changed their minds, largely due to the increasing evidence of safety. The purpose of this review was to gather all available information to update clinicans. The physiology and pathophysiology underpinning glucose regulation and the management of diabetes in the air allowing certain insulin-treated pilots to fly are discussed.

This dataset includes all thenumpy arrays used to create each figure in the study: "Cloud-Radiation Interactions and their Contributions to Convective Self-Aggregation". Each zipped file contains the arrays used to create one figure. The original scripts used to create the figures from the raw data are included in the python_scripts file. All arrays arein SI units unless stated in the name of the file. Arrays with the file name starting x_axis or y_axis should beused to plot the other arrays against.

Introduction Specific patterns of blood test results are associated with COVID-19 infection. The aim of this study was to identify which blood tests could be used to assist in diagnosing COVID-19. Method A retrospective review was performed on consecutive patients referred to hospital with a clinical suspicion of COVID-19 over a period of four weeks. The patient’s clinical presentation and severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (SARS-CoV-2 RT-PCR) were recorded. The patients were divided by diagnosis into COVID (COVID-19 infection) or CONTROL (an alternate diagnosis). A retrospective review of consecutive patients over a further two-week period was used for the purposes of validation. Results Overall, 399 patients (53% COVID, 47% CONTROL) were analysed. White cell count, neutrophils and lymphocytes were significantly lower, while lactate dehydrogenase and ferritin were significantly higher, in the COVID group in comparison to CONTROL. Combining the white cell count, lymphocytes and ferritin results into a COVID Combined Blood Test (CCBT) had an area under the curve of 0.79. Using a threshold CCBT of –0.8 resulted in a sensitivity of 0.85 and a specificity of 0.63. Analysing this against a further retrospective review of 181 suspected COVID-19 patients, using the same CCBT threshold, resulted in a sensitivity of 0.73 and a specificity of 0.75. The sensitivity was comparable to the SARS-CoV-2 RT PCR. Discussion Mathematically combining the blood tests has the potential to assist clinical acumen allowing for rapid streaming and more accurate patient flow pending definitive diagnosis. This may be of particular use in low-resource settings.

RESUMEN: Este TFG ha tenido como objetivo principal explorar el impacto que tiene la música metal en el turismo. Se determinan las características propias del perfil del consumidor metalero, así como las de los productos y servicios que existen para su disfrute, y se averigua el impacto económico que se genera para otros sectores vinculados. Se presentan las actividades que provocan movimientos turísticos de aficionados a los diferentes festivales existentes, destacando los grandes festivales europeos, y se compara la oferta disponible en diferentes partes del mundo, además de resaltar los principales problemas asociados. A continuación, basándose en una encuesta a aficionados y en entrevistas a integrantes de festivales y bandas, se explora el perfil del consumidor, analizando sus motivaciones, su poder adquisitivo, la fidelidad que presenta y su comportamiento antes, durante y después del espectáculo, para así poder mostrar una imagen representativa de la comunidad metalera. Finalmente, se presentan conclusiones sobre el tema objeto de estudio a raíz de la investigación realizada. ABSTRACT: This TFG seeks to explore the impact that metal music has on tourism, to determine the characteristics of the metal consumer, to present the existing products and services available, and to find out the economic impact that it generates for other related sectors. The activities that encourage tourists to move within the existing festivals are presented, and the major European festivals are highlighted. The metal festival offer from all over the world is analysed together with the main problems associated with them. Based on a questionnaire aimed at metalheads and bands, the profile of the consumer is explored, including their motives, financial situation, loyalty and behaviour before, during and after the event in order to present a clear image of the metal community. Finally, conclusions on the subject under discussion are presented as a result of the investigation that has been carried out. Grado en Gestión Hotelera y Turística

Primary care providers (PCPs) play an important role in providing medical care for patients with type 2 diabetes. Advancements in diabetes technologies can assist PCPs in providing personalised care that addresses each patient’s individual needs. Diabetes technologies fall into two major categories: devices for glycaemic self-monitoring and insulin delivery systems. Monitoring technologies encompass self-measured blood glucose (SMBG), where blood glucose is intermittently measured by a finger prick blood sample, and continuous glucose monitoring (CGM) devices, which use an interstitial sensor and are capable of giving real-time information. Studies show people using real-time CGM have better glucose control compared to SMBG. CGM allows for new parameters including time in range (the time spent within the desired target glucose range), which is an increasingly relevant real-time metric of glycaemic control. Insulin pens have increased the ease of administration of insulin and connected pens that can calculate and capture data on dosing are becoming available. There are a number of websites, software programs, and applications that can help PCPs and patients to integrate diabetes technology into their diabetes management schedules. In this article, we summarise these technologies and provide practical information to inform PCPs about utility in their clinical practice. The guiding principle is that use of technology should be individualised based on a patient’s needs, desires, and availability of devices. Diabetes technology can help patients improve their clinical outcomes and achieve the quality of life they desire by decreasing disease burden.KEY MESSAGESIt is important to understand the role that diabetes technologies can play in primary care to help deliver high-quality care, taking into account patient and community resources. Diabetes technologies fall into two major categories: devices for glycaemic self-monitoring and insulin delivery systems. Modern self-measured blood glucose devices are simple to use and can help guide decision making for self-management plans to improve clinical outcomes, but cannot provide “live” data and may under- or overestimate blood glucose; patients’ monitoring technique and compliance should be reviewed regularly. Importantly, before a patient is provided with monitoring technology, they must receive suitably structured education in its use and interpretation.Continuous glucose monitoring (CGM) is now standard of care for people with type 1 diabetes and people with type 2 diabetes on meal-time (prandial) insulin. Real-time CGM can tell both the patient and the healthcare provider when glucose is in the normal range, and when they are experiencing hyper- or hypoglycaemia. Using CGM data, changes in lifestyle, eating habits, and medications, including insulin, can help the patient to stay in a normal glycaemic range (70–180 mg/dL). Real-time CGM allows for creation of an ambulatory glucose profile and monitoring of time in range (the time spent within target blood glucose of 70–180 mg/dL), which ideally should be at least 70%; avoiding time above range (>180 mg/dL) is associated with reduced diabetes complications and avoiding time below range (180 mg/dL) is associated with reduced diabetes complications and avoiding time below range (

Introduction: HPS is chronic liver disease with impaired oxygenation caused by intrapulmonary shunting(IPS), pulmonary vessel dilation and angiogenesis. Currently only definitive treatment is liver transplantation(LT). Aim: To compare non-invasively derived ventilation/perfusion(VA/Q) and MAA scans to quantify respiratory impairment pre&post LT. Methods: Retrospective study of children meeting diagnostic criteria for HPS between 03/1998-05/2016. Clinical data, MAA and paired SpO2 and FiO2 pre & post LT were collected and ODC constructed to determine VA/Q ratio and R to L IPS. Results: 16 children with HPS with diagnoses of biliary atresia(11), cryptogenic liver disease(2), progressive intrahepatic cholestasis(2) and Alagille syndrome(1). All had SpO2s of ≤94% in air, other lung pathology excluded. HPS diagnosis at median 8.5(IQR 6-12) yrs. Symptoms: exertional dyspnoea(13), dyspnoea at rest(8), cyanosis(10) and oxygen dependency(7). MAA show median (IQR) shunting 18(13-31)% with ODC showing 20(17-25)%. 15 received a LT(1 died on LT list), median age 8.8(7-12) yrs. and waiting time 201(90-382)days. All pulmonary symptoms resolved in median(IQR) 43(14-90)days post LT. Median shunting on ODC pre LT 10(0-24)% & post LT (median 43(17-121)days) was 0(0-0)% p=0.009. Correlation coefficient is 0.91 using mild( Conclusion: Non-invasive ODC and MAA yield comparable results hence are useful in HPS grading in children. R to L IPS reverses with LT with residual pulmonary dysfunction as VA/Q abnormalities persist in same time.

Introduction: BPD is the commonest adverse outcome of premature birth, hence appropriate management is essential. Methods: We undertook a survey of UK neonatal units to determine their management of infants with BPD. Results: Fifty-two neonatal units responded: 37% were level 3 NICUs, 49% level 2 and 14% level 1 units. Sixty percent of units had a BPD management guideline. Thirty-six units used patient triggered ventilation and 14 high frequency oscillatory ventilation. The majority (69%) used volume targeting. Nitric oxide was used by 29.9% of units with no consensus over dosage, range 5-20ppm. Diuretics were used by the majority (64.7%) for fluid overload. They were used routinely by 9.8% of units, reasons included poor weight gain (3.9%) or to facilitate weaning from invasive ventilation (2%). Chlorthiazide, spironolactone and furosemide were the most commonly used diuretics, but in varying combinations. Only 24% of units undertook regular renal ultrasound examinations for infants receiving chronic diuretic therapy. Nineteen units used a course of systemic corticosteroids >9 days, whereas 11 units a course Conclusion: Our survey demonstrates there is no consensus for the management of infants with BPD and emphasizes the need for appropriately designed trials to establish evidence based management.

OBJECTIVE To determine the effect of the sodium–glucose cotransporter 2 inhibitor dapagliflozin on glucose flux, lipolysis, and ketone body concentrations during insulin withdrawal in people with type 1 diabetes. RESEARCH DESIGN AND METHODS A double-blind, placebo-controlled crossover study with a 4-week washout period was performed in 12 people with type 1 diabetes using insulin pump therapy. Participants received dapagliflozin or placebo in random order for 7 days. Stable isotopes were infused to measure the glucose Ra, Rd, and lipolysis. At isotopic steady state, insulin was withdrawn, and the study was terminated after 600 min or earlier if blood glucose reached 18 mmol/L, bicarbonate 5.0 mmol/L. RESULTS At baseline, glucose Ra was significantly higher for the dapagliflozin group than the placebo group. Following insulin withdrawal, plasma glucose concentrations at the end point were significantly lower with dapagliflozin than placebo and glucose Rd area under the curve (AUC)0–180 min and β-hydroxybutyrate (BOHB) AUC0–180 min were significantly higher. There was a small but significantly higher glycerol Ra (measure of lipolysis) AUC0–180 min with dapagliflozin. Nonesterified fatty acid concentrations were not different between treatments. When divided by BMI >27 and CONCLUSIONS During insulin withdrawal, the increase in BOHB with dapagliflozin may be partially due to increased lipolysis. However, reduced renal excretion, reduced BOHB uptake by peripheral tissues, or a metabolic switch to increased ketogenesis within the liver may also play a role.

Objective: To determine the effect of SGLT2 inhibitor dapagliflozin on glucose flux, lipolysis and ketone body concentrations during insulin withdrawal in people with type 1 diabetes. Research Design and Methods: A double-blind placebo controlled crossover study with a 4-week wash out period was performed in 12 people with type 1 diabetes using insulin pump therapy. Participants received dapagliflozin or placebo in random order for 7 days. Stable isotopes were infused to measure the rate of glucose production (Ra), disappearance (Rd) and lipolysis. At isotopic steady state insulin was withdrawn and the study terminated after 600 minutes or earlier if blood glucose reached 18mmol/L, bicarbonate 5.0 mmol/L. Results: At baseline, glucose Ra was significantly higher with dapagliflozin than placebo. Following insulin withdrawal, plasma glucose concentrations at the end point were significantly lower with dapagliflozin than placebo and AUC0-180min glucose Rd and AUC0-180min β-hydroxybutyrate (BOHB) were significantly higher. There was a small but significantly higher AUC0-180min glycerol Ra (measure of lipolysis) with dapagliflozin. Non-esterified fatty acid concentrations were not different between treatments.When divided by BMI>27 and

Introduction Paramedics are employed by Australian and international mining and petroleum organisations to provide emergency medical response, injury prevention, health promotion, chronic disease management, medical referral, primary healthcare and repatriation co-ordination for miners in exploration, construction and production. These are challenging roles given the often isolated, potentially hazardous and clinically unpredictable nature of the sites where these paramedics work. The purpose of this article is to review injuries that occurred in the mining industry with a view to sharing this information with paramedics who work within the mining sector. Methods Data was collected under legislative authority by the Western Australian Department of Mines, Industry Regulation and Safety (DMIRS). Data efficacy was optimised via strong legislative support whereby all organisations involved in mining activities are legally compelled to report to the DMIRS all accidents involving injury. Results A total of 837 injuries were reported during the 6-month period between 1 July and 31 December 2013. These comprised 658 serious injuries, including three fatalities, and 179 minor injuries. Sprains and strains were the most common injury comprising 69% of injuries followed by fractures 10%, lacerations 6%, crushing injuries 5%, bruises and contusions 4%, and dislocations and displacements 2%. Foreign bodies, punctures, bites, amputations, chemical effects, thermal burns, flash and arc burns and loss of consciousness each recorded less than 1% of the injuries. Conclusion Findings presented in this article can be used by paramedics working in the mining sector across Australia and worldwide. Paramedic awareness of the nature and cause of injury is useful for optimally preparing paramedics to perform appropriate diagnosis and treatment and to minimise patient mortality and morbidity.

Author(s): Ford, James S.; Holmes, James F.; Jones, Russell F. | Abstract: Introduction: There is a growing body of literature detailing coronavirus 2019 (COVID-19) cardiovascular complications and hypercoagulability, although little has been published on venous or arterial thrombosis risk.Case Report: In this report, we present a single case of cardioembolic stroke in the setting of COVID-19 related myocarditis, diagnosed via cardiac magnetic resonance imaging and echocardiography. COVID-19 infection was confirmed via a ribonucleic acid polymerase chain reaction assay.Conclusion: Further research is needed to evaluate the hypercoagulable state of patients with COVID-19 to determine whether prophylactic anticoagulation may be warranted to prevent intracardiac thrombi and cardioembolic disease in patients with COVID-19 related myocarditis.

Introduction The aim of this study was to investigate the association between baseline characteristics [HbA1c and body mass index (BMI)] and the effect of mealtime fast-acting insulin aspart (faster aspart) relative to insulin aspart (IAsp) or basal-only insulin therapy on several efficacy and safety outcomes in people with diabetes. Methods Post hoc analysis of three randomised phase 3a trials in people with type 1 diabetes (T1D; onset 1) and type 2 diabetes (T2D; onset 2 and 3). Participants (N = 1686) were stratified according to baseline BMI ( 58– 7.5– 30 kg/m2 subgroup. Conclusions In participants with T1D and T2D, treatment differences (for change in HbA1c and overall hypoglycaemia) between mealtime faster aspart and insulin comparators were similar to the corresponding overall analysis across baseline HbA1c and BMI subgroups. The finding of a lower total daily insulin dose in participants with obesity (BMI > 30 kg/m2) and T1D treated with faster aspart, versus those treated with IAsp, may warrant further investigation. Trial Registration ClinicalTrials.gov NCT01831765 (onset 1); NCT01819129 (onset 2); NCT01850615 (onset 3). Funding Novo Nordisk A/S, Søborg, Denmark. Electronic supplementary material The online version of this article (10.1007/s13300-018-0553-7) contains supplementary material, which is available to authorized users.